- SIX-MEMBERED AND SIX-MEMBERED HETEROCYCLIC COMPOUND AND USES THEREOF SERVING AS PROTEIN RECEPTOR KINASE INHIBITOR
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Provided are a preparation and applications of a six-membered fused with six-membered heterocyclic compound, specifically, provided in the present invention is a compound as represented by formula I as follows, where the definitions of the groups are as described in the description. The compound has TRK kinase inhibiting activity and can serve as a pharmaceutical composition for treating TRK dysfunction-related diseases.
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Paragraph 0106-0109
(2021/09/24)
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- Identification, Characterization, and Optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel Plasmodium falciparum Phosphatidylinositol-4-kinase Inhibitors with in Vivo Efficacy in a Humanized Mouse Model of Malaria
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A novel 2,8-disubstituted-1,5-naphthyridine hit compound stemming from the open access Medicines for Malaria Venture Pathogen Box formed a basis for a hit-to-lead medicinal chemistry program. Structure-activity relationship investigations resulted in compounds with potent antiplasmodial activity against both chloroquine sensitive (NF54) and multidrug resistant (K1) strains of the human malaria parasite Plasmodium falciparum. In the humanized P. falciparum mouse efficacy model, one of the frontrunner compounds showed in vivo efficacy at an oral dose of 4 × 50 mg·kg-1. In vitro mode-of-action studies revealed Plasmodium falciparum phosphatidylinositol-4-kinase as the target.
- Kandepedu, Nishanth,Gonzàlez Cabrera, Diego,Eedubilli, Srinivas,Taylor, Dale,Brunschwig, Christel,Gibhard, Liezl,Njoroge, Mathew,Lawrence, Nina,Paquet, Tanya,Eyermann, Charles J.,Spangenberg, Thomas,Basarab, Gregory S.,Street, Leslie J.,Chibale, Kelly
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p. 5692 - 5703
(2018/06/19)
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- Process for Manufacturing a Naphthyridine Derivative
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The invention relates to a process and synthetic intermediates that can be used for manufacturing the compound of formula (1-6) which is a synthetic intermediate useful in the preparation of antibiotic compounds.
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Paragraph 0110-0112
(2015/02/18)
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- A one-pot diazotation-fluorodediazoniation reaction and fluorine gas for the production of fluoronaphthyridines
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Several synthetic routes to 7-fluoro-2-methoxy-8-methyl-1,5-naphthyridine (1) are presented, and their suitability for scale-up is discussed. The way of introducing the fluorine atom is crucial. Early routes start from commercially available fluorinated building blocks or employ F+ reagents like SelectFluor and delivered up to 70 kg of 7-fluoro-2-methoxy-1,5-naphthyridine (18). To prepare for larger scales, the focus turned to the use of HF or elemental fluorine, both one of the cheapest sources of fluorine. The first method, a one-pot diazotation-fluorodediazoniation with 6-methoxy-1,5- naphthyridin-3-amine (9) in HF gave the fluorinated naphthyridine 18 in high yield and purity without isolation of the unstable diazonium salt, the latter being a severe drawback of the related Balz-Schiemann protocol. The second method relies on the use of fluorine gas for a surprisingly selective ortho-fluorination of 6-methoxy-1,5-naphthyridin-4-ol (10).
- Abele, Stefan,Schmidt, Gunther,Fleming, Matthew J.,Steiner, Heinz
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p. 993 - 1001
(2014/10/15)
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- Aurora Kinase Modulators and Method of Use
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The present invention relates to chemical compounds having a general formula I wherein A1-8, D′, L1, L2, R1, R6-8 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.
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Paragraph 0321
(2014/11/27)
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- PROCESS FOR MANUFACTURING A NAPHTHYRIDINE DERIVATIVE
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The invention relates to a process and synthetic intermediates that can be used for manufacturing the compound of formula (1-6) which is a synthetic intermediate useful in the preparation of antibiotic compounds.
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Page/Page column 18
(2013/08/28)
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- NEW COMPOUNDS
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The invention relates to new naphthyridine derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
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Page/Page column 138
(2013/05/21)
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- BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
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Novel bridged bicyclic compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.
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Page/Page column 84
(2013/03/26)
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- AURORA KINASE MODULATORS AND METHOD OF USE
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The present invention relates to chemical compounds having a general formula I {INSERT STRUCTURE HERE} wherein A1-8, D,, L1, L2, R1, R6-8 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.
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Page/Page column 50
(2008/12/04)
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- Strategic studies in the syntheses of novel 6,7-substituted quinolones and 7- or 6-substituted 1,6- and 1,7-naphthyridones
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This paper describes the different strategies devised and applied to overcome the selectivity issues in the syntheses of 6,7-disubstituted-1H-quinolin-4-one, 7-substituted-1H-1,6-naphthyridin-4-one and 6-substituted-1H-1,7-naphthyridin-4-one derivatives. They allowed us to improve the overall yields and the scaling-up feasibility. Several examples illustrate these strategies with their advantages and drawbacks.
- Morgentin, Rémy,Pasquet, Georges,Boutron, Pascal,Jung, Frédéric,Lamorlette, Maryannick,Maudet, Micka?l,Plé, Patrick
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p. 2772 - 2782
(2008/09/19)
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- Novel pyrazole derivatives as potent inhibitors of type II topoisomerases. Part 1: Synthesis and preliminary SAR analysis
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In an attempt to search for a new class of antibacterial agents, we have discovered a series of pyrazole analogs that possess good antibacterial activity for Gram-positive and Gram-negative organisms via inhibition of type II bacterial topoisomerases. We have investigated the structure-activity relationships of this series, with an emphasis on the length and conformation of the linker. This work led to the identification of tetrahydroindazole analogs, such as compound 1, as the most potent class of compounds.
- Gomez, Laurent,Hack, Michael D.,Wu, Jiejun,Wiener, John J.M.,Venkatesan, Hari,Santillan Jr., Alejandro,Pippel, Daniel J.,Mani, Neelakandha,Morrow, Brian J.,Motley, S. Timothy,Shaw, Karen Joy,Wolin, Ronald,Grice, Cheryl A.,Jones, Todd K.
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p. 2723 - 2727
(2008/02/03)
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- NAPHTHYRIDINE DERIVATIVES
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The invention concerns naphthyridine derivatives of Formula (Ia) or (Ib) or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, G1, G2, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders or disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 153
(2010/11/28)
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- Bicyclic pyrazole compounds as antibacterial agents
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Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.
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Page/Page column 17
(2010/11/24)
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- AMINOPIPERIDINE QUINOLINES AND THEIR AZAISOSTERIC ANALOGUES WITH ANTIBACTERIAL ACTIVITY
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The present invention relates to compounds that demonstrate antibacterial activity, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in warm blooded animals such as humans. In particular this invention relates to compounds useful for the treatment of bacterial infections in warm-blooded animals such as humans, more particularly to the use of these compounds in the manufacture of medicaments for use in the treatment of bacterial infections in warm blooded animals such as humans.
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Page/Page column 85
(2008/06/13)
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- COMPOUND HAVING TGF-BETA INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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The present invention provides compounds of formula (I) or compounds of formula (II) and pharmaceutically acceptable salts or solvates thereof. An objective of the present invention is to provide compounds having TGF2 inhibitory activity.
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Page/Page column 79
(2010/11/24)
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- AMINOCYCLOHEXENE QUINOLINES AND THEIR AZAISOSTERIC ANALOGUES WITH ANTIBACTERIAL ACTIVITY
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Cyclohexene derivatives and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly man.
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Page/Page column 30
(2010/02/06)
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